AB. Santamarina, RG. Moreira, LV. Mennitti, YA. Martins Ferreira, A. Jucá, CM. Prado, et al. (2025). Low-carbohydrate diet enriched with omega-3 and omega-9 fatty acids modulates inflammation and lipid metabolism in the liver and white adipose tissue of a mouse model of obesity. Nutrition, metabolism, and cardiovascular diseases : NMCD, 35(8), 103932. https://doi.org/10.1016/j.numecd.2025.103932

PubMed 40089393

[Abstract]
BACKGROUND AND AIM: The low-carbohydrate high-fat (LCHF) diet lipids are often overlooked for obesity management. We hypothesized that unsaturated lipids enhance fatty acid metabolism, and influence obesity-related metainflammation.

METHODS AND RESULTS: Male Swiss mice were fed an obesity-inducing diet for ten weeks. Subsequently, the obese mice were divided into four groups, each receiving a LCHF diet enriched with different types of lipids: saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA) ω-3, PUFA ω-6, and monounsaturated fatty acids (MUFA) ω-9 during six weeks as an obesity intervention. For comparison, a lean control (CTL) group and an obesity control (HFC) group were also included, spanning the entire 16-week experimental protocol. We evaluated body mass gain, fatty acid profiles via gas chromatography, elongase, and desaturase activities, NFκBp65 expression by western blotting, and cytokine by ELISA kits in serum, liver, and retroperitoneal adipose tissue (RET) samples. Our results highlight that ω-3 and ω-9 LCHF diets facilitate weight loss and enhance unsaturated fatty acid incorporation in liver, RET, and serum compared to the other groups. The ω-3 LCHF diet notably reduced the ω-6/ω-3 ratio and improved inflammatory status by reducing cytokines such as IL-4, IL-17, IL-33, CXCL1/KC, and inhibiting NFκBp65 activity compared to the HFC group. Desaturase (delta-9 desaturase-18, delta-6 desaturase) and elongase (ELOVL5 and ELOVL6) activities were modulated in liver, RET, and serum samples by ω-3 and ω-9 compared to the HFC group.

CONCLUSIONS: ω-3 and ω-9 fats were most effective in obesity treatment with the LCHF diet, highlighting the significance of lipid type in carbohydrate-restriction for obesity management.